Structure determination of the Ras-binding domain of the Ral-specific guanine nucleotide exchange factor Rlf.

Ral-specific guanine nucleotide exchange factors RalGDS, Rgl, and Rlf have been suggested to function as intermediates between Ras and Ral pathways by being able to bind Ras proteins through their C-terminal Ras-binding domains (RBD). The RBDs of RalGDS and of the Ser/Thr kinase c-Raf-1 have been shown to have the ...
same tertiary structure. In contrast to the RBDs of Raf and RalGDS, which bind either Ras or Rap with high affinity, Rlf-RBD has a similar affinity for both GTP-binding proteins. To be able to compare these RBDs on a structural level, we have solved the three-dimensional structure of Rlf-RBD by NMR spectroscopy. The overall tertiary structure of Rlf-RBD shows the betabetaalphabetabetaalphabeta-fold of the ubiquitin superfamily and is very similar to that of RalGDS-RBD. The binding interface of Rlf-RBD to Ras was mapped using chemical shift analysis and indicated a binding mode similar to that in the case of Rap.Raf-RBD. However, comparison of the putatively interacting regions revealed structural differences which are proposed to be responsible for the different substrate affinities of Rlf-, RalGDS-, and Raf-RBD.
Mesh Terms:
Amino Acid Sequence, Animals, Crystallography, X-Ray, GTP-Binding Proteins, Guanine Nucleotide Exchange Factors, Guanylyl Imidodiphosphate, Macromolecular Substances, Mice, Models, Molecular, Molecular Sequence Data, Nuclear Magnetic Resonance, Biomolecular, Protein Binding, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Substrate Specificity, Transcription Factors, ral Guanine Nucleotide Exchange Factor, rap GTP-Binding Proteins, ras Proteins
Biochemistry
Date: Sep. 29, 1998
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